Efficacy and Safety of Influenza Vaccine During Sarcoidosis (SARCOVAC)

This study has been completed.

Sponsor:

Assistance Publique - Hôpitaux de Paris

ClinicalTrials.gov Identifier:

NCT01687517

First Posted: September 19, 2012

Last Update Posted: April 21, 2015

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
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Sarcoidosis is an inflammatory disease of unknown origin that can affect all organs, especially the lungs and mediastinum. Some location of sarcoidosis may require treatment with corticosteroids or immunosuppressors.Although seasonal influenza vaccination can be recommended in sarcoidosis in some subgroups at risk (respiratory failure, pulmonary fibrosis, age over 65, use of immunosuppressive therapy, etc ...), the investigators presently have no data on the efficacy and safety (absence of adverse reactions) of seasonal influenza vaccination in sarcoidosis.Especially it is not known whether the seasonal influenza vaccine provides the same rate and same type of vaccine response in sarcoidosis patients than in the general population. Similarly, it is unclear whether the vaccine response is modified by the severity of the disease and treatment with corticosteroids and immunosuppressors.Based on what is known in systemic lupus and rheumatoid arthritis, which are both inflammatory and autoimmune diseases, the investigators expect at best a 50% vaccine response in patients with sarcoidosis and a 85% vaccination response in healthy controls. The demonstration of a vaccine response could allow reconsidering new vaccine approaches in sarcoidosis.

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

Humoral immunogenicity [ Time Frame: 21 days post-vaccination ]

Humoral immunogenicity of the vaccine will be measured 3 weeks after injection of influenza vaccine (day 21) by comparison of the seroconversion rates between patients with sarcoidosis and the control group of healthy subjects.

Secondary Outcome Measures:

Immunogenicity [ Time Frame: at Day 0, Day 21 and Day 180 ]

Effect of the initial clinical phenotype (including disease activity score) on the seroconversion and seroprotection rates, and the seroconversion factor, at each visit

Clinical phenotype [ Time Frame: at Day 21 and Day 180 ]

Descriptive study of the evolution of clinical phenotype (eg, severity of illness) after vaccination at D21 and D180

Auto immunity activity [ Time Frame: At Day 0, at Day 21 and at 6 months post-vaccination ]

Comparison of autoantibody levels before and after vaccination (anti-nuclear total, rheumatoid factor, anti-GM1 measured at D0, D21 and D180) in all individuals included in the study.

Effect of therapy on immunogenicity [ Time Frame: at Day 21 and Day 180 ]

Effect of the dose of corticosteroids and immunosuppressive therapy on the seroconversion and seroprotection rates and seroconversion factor at D21 and D180;

Immunogenicity between groups [ Time Frame: at Day 0, Day 21 and Day 180 ]

Comparison of the seroprotection rate and the seroconversion factor between patients with sarcoidosis and the control group of healthy subjects at D21 and D180 post-vaccination.

Long term immune response [ Time Frame: At 6 months post-vaccination ]

Comparison of the persistence of the immune response between patients with sarcoidosis and control subjects at D180

Lymphocytes subpopulations analysis [ Time Frame: At Day 0 and at 21 days post-vaccination ]

Comparison between D0 and D21 of the distributions in absolute values and percentages of circulating lymphocyte subpopulations, in particular mucosal "homing" CD4+ lymphocytes, in all individuals included in the study;

Regulatory T Lymphocytes [ Time Frame: At Day 0 and Day 21 ]

Effect of the regulatory T cells titers on the seroconversion and seroprotection rates, and the seroconversion factor at D0

Disease activity evolution [ Time Frame: at Day 0, Day 21 and Day 180 ]

Effect of the CD4+-CD103+ T cells + at J0 and its evolution between J0 and J21 days based on the scalability of sarcoidosis evaluated by 1/changes in serum enzyme angiotensin converting, IgG, IgA IgM,; 2/ the comparative pulmonary radiological changes and 3/ the in pulmonary function changes between day 0 and day 180.

Other immune response [ Time Frame: Between Day 0 to 6 months post-vaccination ]

Seroprevalence and comparison between D0 and D180 of anti-diphtheria toxin and anti-tetanus toxin in all individuals included.

Drug: Seasonal influenza vaccine available for the 2012-2013 vaccine campaign

Single injection of the vaccine at D0 (0.5mL intra-muscularly or subcutaneous for patient under anticoagulant treatment)

Active Comparator: Volunteer

100 volunteers

Drug: Seasonal influenza vaccine available for the 2012-2013 vaccine campaign

Single injection of the vaccine at D0 (0.5mL intra-muscularly or subcutaneous for patient under anticoagulant treatment)

Detailed Description:

Data on vaccination in sarcoidosis are largely insufficient. It is thus unclear whether the vaccine response is modified according to the clinical phenotype of the disease and/or treatment with corticosteroids and immunosuppressants. However, sarcoidosis is accompanied by numerous disturbances of the immune system, including a tendency to anergy which may affect the efficacy of the vaccine, especially when the disease is active and severe. In addition, the tolerance of influenza vaccination in patients with sarcoidosis has not been studied yet.The influenza vaccination in sarcoidosis is a common practice among medical specialists who care for patients with sarcoidosis, either internists or lung specialists.. However, the practice of this vaccination is not based on scientific evidence, because there are no data establishing the efficacy and safety of influenza vaccination in sarcoidosis.Thus, it is possible that the influenza vaccine is less immunogenic in patients with sarcoidosis than in healthy adults, which may reduce the clinical effectiveness of vaccination. It therefore seems essential to determine the efficacy and safety of this vaccine, which is widely practiced. Poor efficiency could lead to the development of different vaccination strategies, based in particular on the administration of adjuvanted vaccines.

Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:

18 Years to 65 Years (Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria for patients:

Age ≥ 18 and ≤ 65;

Signature of informed consent

Follow-up : six months following the influenza vaccination at D0

Sarcoidosis diagnosed and histologically proven since at least 6 months

unchanged treatment of Sarcoidosis for at least 3 months, except for the case of a decrease in doses of corticosteroids and at a stable dose of immunosuppressive drugs

Central nervous system impairment and / or device and confirmed with clinical impact and abnormal imaging and / or electromyogram- Renal impairment (histologically confirmed) responsible for a decrease in creatinine clearance

disabling Lupus pernio

Sinuso-nasal and / or laryngeal impairment histologically confirmed

Disseminated impairment, ie affecting more than four organs

Dose of corticosteroids ≥to 10 mg per day of the equivalent of prednisone or the necessity of an immunosuppressive therapy (with the exception of Rituximab) to control sarcoidosis- Existence of an associated metabolic disorder